Associations of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation: The Atherosclerosis Risk in Communities Study

Background We examined the relationships of anger, vital exhaustion, anti-depressant use, and poor social ties with incident atrial fibrillation in a biracial cohort of middle and older-aged adults. Methods This analysis included 11,445 Atherosclerosis Risk in Communities Study participants who were free of atrial fibrillation at baseline in 1990–1992. Vital exhaustion was assessed at baseline and defined as a score in the highest quartile on the 21-item Vital Exhaustion Questionnaire. Baseline anti-depressant use was self-reported. The Spielberger Trait Anger Scale to assess anger and both the Interpersonal Support Evaluation List and the Lubben Social Network Scale to assess social ties were also administered at baseline. The primary outcome was incident atrial fibrillation throughout 2016, identified by electrocardiogram, hospital discharge coding of atrial fibrillation, and death certificates. Results A total of 2220 incident atrial fibrillation cases were detected over a median follow-up of 23.4 years. After adjusting for age, race-center, sex, education, and height, participants in the 4th Vital Exhaustion Questionnaire quartile (referent = 1st Vital Exhaustion Questionnaire quartile) and those reporting anti-depressant use were at increased risk for atrial fibrillation (hazard ratio = 1.45, 95% confidence interval 1.29–1.64 for Vital Exhaustion Questionnaire; hazard ratio = 1.37, 95% confidence interval 1.11–1.69 for anti-depressant use). The increased atrial fibrillation risk observed for 4th Vital Exhaustion Questionnaire quartile participants remained significant after additional adjustment for relevant comorbidities (hazard ratio = 1.20; confidence interval 1.06–1.35). No significant associations were observed for anger or poor social ties with development of atrial fibrillation. Conclusions Vital exhaustion is associated with an increased risk of incident atrial fibrillation.

Download Full-text

Migraine with visual aura is a risk factor for incident atrial fibrillation

Neurology ◽

10.1212/wnl.0000000000006650 ◽

2018 ◽

Vol 91 (24) ◽

pp. e2202-e2210 ◽

Cited By ~ 24

Author(s):

Souvik Sen ◽

X. Michelle Androulakis ◽

Viktoriya Duda ◽

Alvaro Alonso ◽

Lin Yee Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Visual Aura ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk

ObjectiveMigraine with visual aura is associated with cardioembolic stroke risk. The aim of this study was to test association between migraine with visual aura and atrial fibrillation (AF), in the Atherosclerosis Risk in Communities study.MethodsIn the Atherosclerosis Risk in Communities study, a longitudinal, community-based cohort study, participants were interviewed for migraine history in 1993–1995 and were followed for incident AF through 2013. AF was adjudicated using ECGs, discharge codes, and death certificates. Multivariable Cox proportional hazards models were used to study the relation between migraine and its subtypes with incident AF, compared with controls without headaches. Mediation analysis was conducted to test whether AF was a mediator of migraine with visual aura-associated stroke risk.ResultsOf 11,939 participants assessed for headache and without prior AF or stroke, 426 reported migraines with visual aura, 1,090 migraine without visual aura, 1,018 nonmigraine headache, and 9,405 no headache. Over a 20-year follow-up period, incident AF was noted in 232 (15%) of 1,516 with migraine and 1,623 (17%) of 9,405 without headache. After adjustment for multiple confounders, migraine with visual aura was associated with increased risk of AF compared to no headache (hazard ratio 1.30, 95% confidence interval 1.03–1.62) as well as when compared to migraine without visual aura (hazard ratio 1.39, 95% confidence interval 1.05–1.83). The data suggest that AF may be a potential mediator of migraine with visual aura–stroke risk.ConclusionsMigraine with aura was associated with increased risk of incident AF. This may potentially lead to ischemic strokes.

Download Full-text

Vital exhaustion and sudden cardiac death in the Atherosclerosis Risk in Communities Study

Heart ◽

10.1136/heartjnl-2017-311825 ◽

2017 ◽

Vol 104 (5) ◽

pp. 423-429 ◽

Cited By ~ 2

Author(s):

Brittany M Bogle ◽

Nona Sotoodehnia ◽

Anna M Kucharska-Newton ◽

Wayne D Rosamond

Keyword(s):

Risk Factors ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Disease Risk ◽

Ventricular Tachyarrhythmia ◽

Atherosclerosis Risk In Communities ◽

Vital Exhaustion ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

ObjectiveVital exhaustion (VE), a construct defined as lack of energy, increased fatigue and irritability, and feelings of demoralisation, has been associated with cardiovascular events. We sought to examine the relation between VE and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsThe ARIC Study is a predominately biracial cohort of men and women, aged 45–64 at baseline, initiated in 1987 through random sampling in four US communities. VE was measured using the Maastricht questionnaire between 1990 and 1992 among 13 923 individuals. Cox proportional hazards models were used to examine the hazard of out-of-hospital SCD across tertiles of VE scores.ResultsThrough 2012, 457 SCD cases, defined as a sudden pulseless condition presumed due to a ventricular tachyarrhythmia in a previously stable individual, were identified in ARIC by physician record review. Adjusting for age, sex and race/centre, participants in the highest VE tertile had an increased risk of SCD (HR 1.48, 95% CI 1.17 to 1.87), but these findings did not remain significant after adjustment for established cardiovascular disease risk factors (HR 0.94, 95% CI 0.73 to 1.20).ConclusionsAmong participants of the ARIC study, VE was not associated with an increased risk for SCD after adjustment for cardiovascular risk factors.

Download Full-text

Abstract MP48: Social Network, Social Support, and the Risk of Incident Stroke: The Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.129.suppl_1.mp48 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Mako Nagayoshi ◽

Susan A Everson-Rose ◽

Hiroyasu Iso ◽

Thomas H Mosley ◽

Kathryn M Rose ◽

...

Keyword(s):

Social Support ◽

Social Network ◽

Short Form ◽

Network Size ◽

Community Dwelling ◽

Men And Women ◽

Atherosclerosis Risk In Communities ◽

Vital Exhaustion ◽

Increased Risk ◽

Atherosclerosis Risk

Background and Purpose: Having a small social network and lack of social support have been associated with incident coronary heart disease, but little is known about their association with incident stroke. Thus, we assessed the association of a small social network and lack of social support with risk of incident stroke and evaluated whether the relation was mediated by vital exhaustion and inflammation. Methods: The Atherosclerosis Risk in Communities (ARIC) Study measured social network and social support in 13,686 men and women (mean, 57 ± 5.7 years, 56% female, 24% black; 76% white) initially free of stroke. The 10-item Lubben Social Network Scale and 16-item Interpersonal Support Evaluation List-Short Form were used to assess social network size and social support, respectively. Results: Over a median follow-up of 18.6-years, 905 incident strokes occurred. Relative to participants with a large social network, those with a small social network had a higher risk of stroke [HR (95% CI): 1.43 (1.03-2.00)] after adjustment for demographic and socioeconomic characteristics and marital status ( Table ). Further adjustment for other potential confounders attenuated the association slightly. Vital exhaustion, but not inflammation, partly mediated the association between a small social network and stroke. Social support was unrelated to incident stroke. Conclusions: In this sample of US community-dwelling men and women, having a small social network was associated with excess risk of incident stroke. As with other cardiovascular conditions, having a small social network appears to be associated with modestly increased risk of incident stroke.

Download Full-text

Abstract 47: Atrial Fibrillation is Associated With Increased Risk of Incident Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.135.suppl_1.47 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Pamela L Lutsey ◽

Faye L Norby ◽

Alvaro Alonso ◽

Mary Cushman ◽

Lin Y Chen ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Incidence Rate ◽

Case Reports ◽

Time Dependent ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Shared Risk

Background: It is well-established that atrial fibrillation (AF) is associated with thrombus formation in the left atrium, which can lead to ischemic stroke. Case reports, autopsies, and transesophageal echo data have indicated that clot formation also occurs in the right atrium (i.e. right-side intracardiac thrombosis) of AF patients, which could lead to pulmonary embolism (PE). However, it is unclear whether this occurrence is common. Objective: Test the hypotheses that individuals with incident AF are at elevated risk of developing venous thromboembolism (VTE), and that the association will be stronger for those presenting with PE alone versus PE and deep vein thrombosis (DVT) or DVT alone. Methods: A total of 15,205 Atherosclerosis Risk in Communities (ARIC) study participants, aged 45-64 years, were followed from baseline (1987-1989) to 2011 for incidence of AF and VTE (median follow-up 19.8 years). Incident AF and VTE events were identified via active surveillance and defined by relevant hospital discharge ICD codes. VTE events were validated by medical record review. Multivariable-adjusted Cox proportional hazards regression models were used, with AF modeled as a time-dependent covariate. We also evaluated separately risk of PE without evidence of DVT, DVT without PE, and events presenting with both PE and DVT. Results: At baseline participants were on average 54 years old, 55% female and 26% black. In the absence of AF there were 678 VTE events, for an incidence rate of 2.6 per 1000 person-years. After an AF diagnosis there were 77 events, with an incidence rate of 7.1 per 1000 person-years. In multivariable-adjusted models, having AF (versus no AF) was associated with a greater risk of incident VTE; the HR (95% CI) was 2.10 (1.65-2.68) after adjustment for demographics, 1.82 (1.42-2.32) additionally accounting for numerous AF and VTE risk factors, and 1.97 (1.53-2.53) after further adjusting for time-dependent anticoagulant use. When we restricted to PE events without evidence of DVT there were 188 events in total, of which 19 occurred following a diagnosis of AF. The HR for AF (versus no AF) was 1.53 (0.92-2.56) in fully adjusted models. For DVT alone there were 384 events in total, of which 48 occurred after AF diagnosis; the HR for AF was 2.43 (1.77-3.33). Among the 116 events presenting with both DVT and PE, 10 occurred after AF diagnosis, and the HR for AF was 1.36 (0.67-2.75). Conclusions: Diagnosis with AF was associated with a nearly 2-fold increased risk of incident VTE. The association was not stronger when isolated to those with PE without DVT, suggesting that higher risk of VTE among AF patients may be due to either the coagulation abnormalities that accompany AF, or shared risk factors that were not fully accounted for in this analysis.

Download Full-text

Abstract 79: Troponin T, NT-proBNP, and Incidence of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study

Stroke ◽

10.1161/str.44.suppl_1.a79 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Aaron R Folsom ◽

Vijay Nambi ◽

Elizabeth J Bell ◽

Oludamilola W Oluleye ◽

Rebecca F Gottesman ◽

...

Keyword(s):

Ischemic Stroke ◽

General Population ◽

Troponin T ◽

High Sensitivity ◽

Hazard Ratio ◽

Cardioembolic Stroke ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

Increased levels of plasma troponins and natriuretic peptides in the general population are associated with increased future risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, the Atherosclerosis Risk in Communities (ARIC) Study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke. We measured plasma high-sensitivity TnT and NT-proBNP in 10,902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507). Analyses were performed using proportional hazards modeling. Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially, cardioembolic stroke, but not with lacunar or hemorrhagic stroke. After adjustment for other stroke risk factors, the hazard ratio (95% CI) per one SD greater increment of natural log-transformed TnT was 1.23 (1.13, 1.35) for total stroke, 1.27 (1.15, 1.40) for total ischemic stroke, and 1.36 (1.14, 1.62) for cardioembolic stroke. Likewise, the hazard ratio per one SD greater natural log-transformed NT-proBNP, was 1.37 (1.26, 1.49) for total stroke, 1.39 (1.27, 1.53) for total ischemic stroke, and 1.95 (1.67, 2.28) for cardioembolic stroke. The hazard ratios for jointly high values of TnT (≥0.013 ug/L) and NT-proBNP (≥155.2 pg/mL), versus neither biomarker high, were 2.70 (1.92, 3.79) for total stroke and 6.26 (3.40, 11.5) for cardioembolic stroke, and somewhat stronger for NT-proBNP than TnT. Strikingly, approximately 58% of cardioembolic strokes occurred in the highest quintile of pre-stroke NT-proBNP (versus 3% occurring in the lowest quintile), and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence. In conclusion, in the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.

Download Full-text

Physical activity modifies the risk of atrial fibrillation in obese individuals: The HUNT3 study

European Journal of Preventive Cardiology ◽

10.1177/2047487318784365 ◽

2018 ◽

Vol 25 (15) ◽

pp. 1646-1652 ◽

Cited By ~ 14

Author(s):

Lars E Garnvik ◽

Vegard Malmo ◽

Imre Janszky ◽

Ulrik Wisløff ◽

Jan P Loennechen ◽

...

Keyword(s):

Physical Activity ◽

Atrial Fibrillation ◽

Body Mass Index ◽

Confidence Interval ◽

Body Mass ◽

High Body Mass Index ◽

Overweight And Obesity ◽

Hazard Ratio ◽

Increased Risk

Background Atrial fibrillation is the most common heart rhythm disorder, and high body mass index is a well-established risk factor for atrial fibrillation. The objective of this study was to examine the associations of physical activity and body mass index and risk of atrial fibrillation, and the modifying role of physical activity on the association between body mass index and atrial fibrillation. Design The design was a prospective cohort study. Methods This study followed 43,602 men and women from the HUNT3 study in 2006–2008 until first atrial fibrillation diagnosis or end of follow-up in 2015. Atrial fibrillation diagnoses were collected from hospital registers and validated by medical doctors. Cox proportional hazard regression analysis was performed to assess the association between physical activity, body mass index and atrial fibrillation. Results During a mean follow-up of 8.1 years (352,770 person-years), 1459 cases of atrial fibrillation were detected (4.1 events per 1000 person-years). Increasing levels of physical activity were associated with gradually lower risk of atrial fibrillation ( p trend 0.069). Overweight and obesity were associated with an 18% (hazard ratio 1.18, 95% confidence interval 1.03–1.35) and 59% (hazard ratio 1.59, 95% confidence interval 1.37–1.84) increased risk of atrial fibrillation, respectively. High levels of physical activity attenuated some of the higher atrial fibrillation risk in obese individuals (hazard ratio 1.53, 95% confidence interval 1.03–2.28 in active and 1.96, 95% confidence interval 1.44–2.67 in inactive) compared to normal weight active individuals. Conclusion Overweight and obesity were associated with increased risk of atrial fibrillation. Physical activity offsets some, but not all, atrial fibrillation risk associated with obesity.

Download Full-text

Association of Atrial Fibrillation With Incidence of Extracranial Systemic Embolic Events: The ARIC Study

Journal of the American Heart Association ◽

10.1161/jaha.120.016724 ◽

2020 ◽

Vol 9 (18) ◽

Author(s):

Mengyuan Shi ◽

Lin Y. Chen ◽

Wobo Bekwelem ◽

Faye L. Norby ◽

Elsayed Z. Soliman ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cox Regression ◽

Adverse Outcomes ◽

Hospital Discharges ◽

Atherosclerosis Risk In Communities ◽

Entire Cohort ◽

Point Increase ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Aric Study

Background Atrial fibrillation (AF) increases the risk of stroke and extracranial systemic embolic events (SEEs), but little is known about the magnitude of the association of AF with SEE. Methods and Results This analysis included 14 941 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 54.2±5.8, 55% women, 74% White) without AF at baseline (1987–1989) followed through 2017. AF was identified from study ECGs, hospital discharges, and death certificates, while SEEs were ascertained from hospital discharges. CHA 2 DS 2 ‐VASc was calculated at the time of AF diagnosis. Cox regression was used to estimate associations of incident AF with SEE risk in the entire cohort, and between CHA 2 DS 2 ‐VASc score and SEE risk in those with AF. Among eligible participants, 3114 participants developed AF and 270 had an SEE (59 events in AF). Incident AF was associated with increased risk of SEE (hazard ratio [HR], 3.58; 95% CI, 2.57–5.00), after adjusting for covariates. The association of incident AF with SEE was stronger in women (HR, 5.26; 95% CI, 3.28–8.44) than in men (HR, 2.68; 95% CI, 1.66–4.32). In those with AF, higher CHA 2 DS 2 ‐VASc score was associated with increased SEE risk (HR per 1‐point increase, 1.24; 95% CI, 1.05–1.47). Conclusions AF is associated with more than a tripling of the risk of SEE, with a stronger association in women than in men. CHA 2 DS 2 ‐VASc is associated with SEE risk in AF patients, highlighting the value of the score to predict adverse outcomes and guide treatment decisions in people with AF.

Download Full-text

Abstract P004: Impact of Atrial Fibrillation on Healthcare Utilization in the Community: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.129.suppl_1.p004 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Lindsay G Smith ◽

Pamela L Lutsey ◽

Laura R Loehr ◽

Anna Kucharska-Newton ◽

Lin Y Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Healthcare Utilization ◽

Fee For Service ◽

Atherosclerosis Risk In Communities ◽

Cardiovascular Comorbidities ◽

Increased Risk ◽

Atherosclerosis Risk ◽

Adjusted Rate ◽

Aric Study ◽

The Impact

Background: Atrial fibrillation (AF) is associated with increased risk of hospitalization. However, little is known about the impact of AF on non-inpatient healthcare utilization or about sex or race differences in AF-related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results: ARIC cohort participants with incident AF enrolled in fee-for-service Medicare, Parts A and B, for at least 12 continuous months between 1991 and 2009 were matched on age, sex, race and center to up to three participants without AF. Healthcare utilization was ascertained from inpatient and outpatient Medicare claims and classified based on primary ICD-9 code. The analysis included 944 AF and 2,761 non-AF participants. The average number of days hospitalized per year was 13.1 (95% confidence interval [CI]: 11.5-15.0) and 2.8 (95% CI: 2.5-3.1) for those with and without AF, respectively. The corresponding number of outpatient claims per year was 53.2 (95% CI: 50.4-56.1) and 23.0 (95% CI: 22.2-23.8) for those with and without AF, respectively (Table). Most utilization in AF patients was attributable to non-AF conditions, particularly other-cardiovascular disease (CVD)-related reasons; the adjusted rate ratio for days hospitalized per year for other-CVD-related reasons was 4.76 (95% CI: 3.51 - 6.44) for those with compared to those without AF. There was suggestive evidence that sex modified the association between AF and inpatient utilization, with AF related to greater utilization in women than men. The association between AF and healthcare utilization was similar in whites and blacks. Conclusions: This study highlights the considerably greater healthcare utilization (inpatient and outpatient) among those with AF; the differential in utilization due to other-CVD-related reasons was substantial. In addition to recommended heart rate or rhythm treatment, accompanying cardiovascular comorbidities should be evaluated and managed.

Download Full-text

Low testosterone levels are predictive for incident atrial fibrillation and ischaemic stroke in men, but protective in women – results from the FINRISK study

European Journal of Preventive Cardiology ◽

10.1177/2047487318778346 ◽

2018 ◽

Vol 25 (11) ◽

pp. 1133-1139 ◽

Cited By ~ 16

Author(s):

Tanja Zeller ◽

Renate B Schnabel ◽

Sebastian Appelbaum ◽

Francisco Ojeda ◽

Filip Berisha ◽

...

Keyword(s):

Atrial Fibrillation ◽

Confidence Interval ◽

Ischaemic Stroke ◽

Cox Regression ◽

Experimental Studies ◽

Hazard Ratio ◽

Total Testosterone ◽

Testosterone Levels ◽

Increased Risk ◽

Low Testosterone

Background Atrial fibrillation is the most common serious abnormal heart rhythm, and a frequent cause of ischaemic stroke. Recent experimental studies, mainly in orchiectomised rats, report a relationship between sex hormones and atrial electrophysiology and electroanatomy. We aimed to evaluate whether low testosterone levels are predictive for atrial fibrillation and/or ischaemic stroke in men and women. Design and methods The serum total testosterone levels were measured at baseline in a population cohort of 7892 subjects (3876 male, 4016 female), aged 25–74 years, using a commercially available immunoassay. The main outcome measure was atrial fibrillation or ischaemic stroke, whichever came first. Results During a median follow-up of 13.8 years, a total of 629 subjects (8.0%) suffered from incident atrial fibrillation ( n = 426) and/or ischemic stroke ( n = 276). Cox regression analyses, adjusted for age (used as time-scale), geographical region, total cholesterol (log), high-density lipoprotein-cholesterol (log), hypertension medication, known diabetes, smoking status, waist-hip-ratio, and time of blood drawn, documented differential predictive value of low sex-specific testosterone levels for atrial fibrillation and/or ischaemic stroke, in men and in women: Increasing levels were associated with lower risk in men (hazard ratio per one nmol/l increase 0.98 (95% confidence interval 0.93–1.00); p = 0.049). On the other hand, increasing testosterone levels were associated with higher risk in women (hazard ratio per one nmol/l increase 1.17 (95% confidence interval 1.02–1.36); p = 0.031). Conclusion Our study indicates that low testosterone levels are associated with increased risk of future atrial fibrillation and/or ischaemic stroke in men, while they are protective in women.

Download Full-text

Association between Circulating Protein C Levels and Incident Dementia: The Atherosclerosis Risk in Communities Study

Neuroepidemiology ◽

10.1159/000516287 ◽

2021 ◽

pp. 1-10

Author(s):

Adrienne Tin ◽

Keenan A. Walker ◽

Jan Bressler ◽

B. Gwen Windham ◽

Michael Griswold ◽

...

Keyword(s):

Risk Factors ◽

Confidence Interval ◽

Protein C ◽

Late Life ◽

Hazard Ratio ◽

Inverse Association ◽

Atherosclerosis Risk In Communities ◽

Incident Dementia ◽

Atherosclerosis Risk

Introduction: Hemostasis depends on the delicate balance between coagulants and anticoagulants. Higher levels of circulating coagulants have been associated with higher risk of cerebral infarctions and dementia. In contrast, higher levels of circulating protein C, an endogenous anticoagulant, have been associated with lower risk of cerebral infarctions, and the association between protein C levels and the risk of dementia is unknown. The goal of this study was to evaluate the association of circulating protein C levels in midlife and late life with incident dementia. Methods: Circulating protein C levels were measured using blood samples collected at the midlife baseline (1987–1989) and the late-life baseline (2011–2013) among 14,462 and 3,614 participants, respectively, in the Atherosclerosis Risk in Communities study. Protein C levels were measured using enzyme-linked immunosorbent assay at midlife and a modified aptamer-based assay at late life. Participants were followed up to 2013 from midlife and up to 2017 from late life. Incident dementia was ascertained during the follow-up periods using in-person cognitive and functional assessment, informant interviews, and International Classification of Diseases codes at hospitalization discharge and on death certificates. Cause-specific Cox regression models were used to evaluate the association between quintiles of circulating protein C and incident dementia. Results: From midlife (mean age of 54), 1,389 incident dementia events were observed over a median follow-up of 23 years. From late life (mean age of 75), 353 incident dementia events were observed over a median follow-up of 4.9 years. At both midlife and late life, circulating protein C had an inverse association with incident dementia after adjusting for demographic, vascular, and hemostatic risk factors, incident stroke as time-dependent covariate, and incorporating stabilized weights based on propensity scores (quintile 5 vs. quintile 1 as the reference, midlife hazard ratio 0.80, 95% confidence interval 0.66–0.96, p value for trend 0.04; late-life hazard ratio 0.84, 95% confidence interval: 0.55–1.28, p value for trend 0.04). Discussion/Conclusion: Circulating protein C has an inverse association with incident dementia independent of established risk factors, including stroke. Our results suggest studying anticoagulants in addition to coagulants can increase our understanding on the relationship between hemostasis and dementia.

Download Full-text